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Abstract Because of similar astronomical background, Marine Isotope Stage (MIS) 11 is viewed as an analogue of the Holocene, but the evolution of seasonal climatic instability during MIS 11 has not been well investigated. Here we present a time series of land-snail eggs—a recently-developed proxy of seasonal cooling events—from the Chinese Loess Plateau (CLP) to investigate seasonal climatic instability during MIS 11 and adjacent glacials. Due to the impact of low temperatures on egg hatching, egg-abundance peaks document seasonal cooling events. A total of five egg-abundance peaks were recorded in the CLP during MIS 12, MIS 11 and MIS 10. Three peaks are strong and occur close to glacial inception or interglacial-to-glacial transition; two weaker peaks occur during MIS11. These peaks imply seasonal climatic instability intensifies mainly during glacial initiation or transition. All these events correspond to ice-sheet growth and the loss of ice-rafted debris at high northern latitudes. Moreover, they occurred at the minima of local spring insolation during the MIS 12 and MIS 10 glacials, but at the maxima during the MIS 11 interglacial. This may contribute to the difference in the intensity of seasonal cooling events between low-eccentricity glacials and interglacials. Our results provide new evidence for understanding low-eccentricity interglacial–glacial evolution.

Scientists have been puzzled by the disparity between climate simulations of the past 12,000 years and geological records. Dong et al. reconstructed past annual and seasonal temperatures from land snail records to examine the potential seasonal bias.

Abstract Fluctuations in monsoonal climate on orbital‐ to millennial‐timescales have had a major impact on vegetation change in East Asia since the last deglaciation. However, the influence of centennial‐scale oscillations on the spatio‐temporal characteristics of vegetation and climate during the last deglaciation remains controversial. We present a well‐dated, decadal‐resolution pollen record from the sediments of annually laminated Lake Xiaolongwan in Northeast Asia, which reveals major orbital‐/millennial‐scale and minor quasi‐periodic, that is, ∼500‐year (yr) cyclic, vegetation changes from ∼19.96 to ∼10.79 Kyr ago (covering the last deglaciation). The ∼500‐yr cycles are characterized by alternations in broadleaved forest/boreal coniferous forest with tundra steppe representing warm and humid/cold and dry phases of the monsoonal climate. This cyclicity may be related to El Niño‐like/La Niña‐like state and low‐latitude atmosphere‐ocean processes, against the background of the long‐term trend of the deglacial climatic evolution. Our findings demonstrate a close relationship between ecosystem succession and climate change on centennial scale.

The magnitude and rate of the expansion of the East Asian summer monsoon (EASM) rain belt under future climatic warming are unclear. Appropriate ecological proxy data may provide an improved understanding of the spatial extension of the EASM during past warming intervals. We reconstructed the spatiotemporal pattern of the extension of the EASM since the Last Glacial Maximum (LGM), using six well-dated mollusk fossil sequences from Chinese loess sections located on the modern northern edge of the EASM. The abundance of typical dominant mollusk species indicative of EASM intensity shows a delayed response, from ∼17 ka in the southeastern sections to ∼9 ka in the northwestern sections, during the last deglacial warming. Isoline plots based on a mollusk data synthesis show that the mollusk EASM indicators have a northeast–southwest zonal distribution for both the present-day, the cold LGM, and the warm mid-Holocene, which is consistent with the spatial pattern of modern precipitation. The resulting estimated expansion rate of EASM intensity accelerated during ∼12–9 ka (∼50 km/ka), which corresponds to the early Holocene interval of rapid climatic warming, a northwestward shift of ∼150 km compared to today. This implies that the northern fringe of the EASM in northern China will become wetter in the coming century, under moderate warming scenarios.

Long-term climate cycles can potentially influence population dynamics, including those of humans. Here, the authors combine climate and archaeological records from Northeast China over the past 8000 years and demonstrate ~500 year cycles in both the monsoon and human activity.

The cascading impacts of climate-driven vegetation change on terrestrial invertebrates via trophic and habitat routes is a matter of outstanding concern. However, the combined responses of plant-animal associations in terrestrial ecosystems have seldom been reported on geological timescales, which raises the important questions of how frequently and to what extent such multi-trophic shifts in taxa have occurred during previous warming scenarios. Here we use a combination of mollusk, palynological, and climatic proxy evidence preserved within loess deposits in the southern Chinese Loess Plateau (CLP) to demonstrate how long-term changes in hydroclimatic dynamics during the past 26 kyr were reflected in the subsequent ecological changes. Specifically, there was a shift from a predominantly cold-tolerant mollusk fauna in a dry-steppe environment under cold-dry conditions during the last glacial, to a predominantly thermal-mesophilous fauna in a meadow-steppe environment under a warm temperate climate in the early-middle Holocene. Warmth-adapted mollusk species such as Opeas striatissimum and Punctum orphana were found to have been associated with several deciduous tree taxa (e.g., Corylus, Quercus, and Pterocarya) in both the Holocene record and in the modern ecosystem (based on surveys of 356 surface-soil plots). This suggests there is a clear ecological interdependency between specific vegetation types and mollusk assemblages. As such, the long-term vegetation-mollusk fossil records highlight the indirect impacts of climate change on terrestrial invertebrate turnover via plant-derived food structure and habitat routes, with major implications for understanding how these ecosystems are likely to respond to future climate changes.

The loess stratigraphic boundary at the Pleistocene/Holocene transition defined by the magnetic susceptibility (MS) has previously been assumed to be synchronous with the Marine Isotope Stage (MIS) 2/1 boundary, and approximately time-synchronous at different sections across the Chinese Loess Plateau (CLP). However, although this assumption has been used as a basis for proxy-age model of Chinese loess deposits, it has rarely been tested by using absolute dating methods. In this study, we applied a single-aliquot regenerative-dose (SAR) protocol to the 45-63 μm quartz grain-size fraction to derive luminescence ages for the last glacial and Holocene sections of three loess sections on a transect from southeast to northwest across the CLP. Based on the 33 closely spaced optically stimulated luminescence (OSL) samples from the three sections, OSL chronologies were established using a polynomial curve fit at each section. Based on the OSL chronology, the timing of the Pleistocene/Holocene boundary, as defined by rapid changes in MS values, is dated at ~10.5 ka, 8.5 ka and 7.5 ka in the Yaoxian section, Jingchuan and Huanxian sections respectively. These results are clearly inconsistent with the MIS 2/1 boundary age of 12.05 ka, and therefore we conclude that the automatic correlation of the Pleistocene/Holocene transition, as inferred from the MS record, with the MIS 2/1 boundary is incorrect. The results clearly demonstrate that the marked changes in MS along the southeast to northwest transect are time-transgressive among the different sites, with the timing of significant paleosol development as indicated by the MS record being delayed by 3-4 ka in the northwest compared to the southeast. Our results suggest that this asynchronous paleosol development during the last deglacial was caused by the delayed arrival of the summer monsoon in the northwest CLP compared to the southeast.

The Neogene eolian deposits in the Chinese Loess Plateau (CLP) are one of the most useful continental deposits for understanding climatic changes. To decipher Late Neogene paleoclimatic changes in the CLP, we present a terrestrial mollusk record spanning the time interval between 7.1 and 3.5 Ma from the western CLP. The results indicate four stages of paleoclimatic evolution: From 7.1 to 6.2 Ma, cold and dry climatic conditions prevailed as evidenced by high values of the total number of cold-aridiphilous (CA) mollusk species and by low values of all of the thermo-humidiphilous (TH) mollusk indices. From 6.2 to 5.4 Ma, the climate remained cold and dry but was not quite as dry as during the preceding phase, as indicated by the dominance of CA mollusks and more TH species and individuals. From 5.4 to 4.4 Ma, a warm and moist climate prevailed, as indicated by high values of the TH species and individuals and by the sparsity of CA species and individuals. From 4.4 to 3.5 Ma, all of the CA indices increased significantly and maintained high values; all of the TH indices exhibit high values from 4.4 to 4.0 Ma, an abrupt decrease from 4.0 Ma and a further increase from 3.7 Ma. The CA species of Cathaica pulveraticula, Cathaica schensiensis, and Pupopsis retrodens are only identified in this stage, indicating that the CA species were diversified and that the climate was becoming drier. Moreover, the CA mollusk group exhibits considerable diversity from 7.1 to 5.4 Ma when a cold, dry climate prevailed; whereas the diversity of the TH group was high during the relatively warm, wet interval from 5.4 to 4.4 Ma. This indicates that variations in the diversity of the CA and TH mollusk groups were closely related to climatic changes during the Late Miocene to Pliocene.

Mollusk remains are abundant in archaeological sites in the Guanzhong Basin of Northwestern China, providing good opportunities for investigations into the use of mollusks by prehistoric humans. Here we report on freshwater gastropod and bivalve mollusks covering the time interval from about 5600 to 4500 cal. yrs BP from sites of Mid-Late Neolithic age. They are identified as Cipangopaludina chinensis and Unio douglasiae, both of which are currently food for humans. The shells are well preserved and have no signs of abrasion. They are all freshwater gastropods and bivalves found in pits without water-reworked deposits and have modern representatives which can be observed in rivers, reservoirs, and paddy fields in the studied region. Mollusk shells were frequently recovered in association with mammal bones, lithic artifacts, and pottery. These lines of evidence indicate that the mollusks are the remains of prehistoric meals. The mollusk shells were likely discarded into the pits by prehistoric humans after the flesh was eaten. However, these mollusk remains may not have been staple food since they are not found in large quantities. Mollusk shell tools and ornaments are also observed. Shell tools include shell knives, shell reaphooks and arrowheads, whereas shell ornaments are composed of pendants and loops. All the shell tools and ornaments are made of bivalve mollusks and do not occur in large numbers. The finding of these freshwater mollusk remains supports the view that the middle Holocene climate in the Guanzhong Basin may have been warm and moist, which was probably favorable to freshwater mollusks growing and developing in the region.

Abstract Respiratory syncytial virus (RSV) is the major cause of bronchiolitis and pneumonia in young children and the elderly. There are currently no approved RSV-specific therapeutic small molecules available. Using high-throughput antiviral screening, we identified an oral drug, the prenylation inhibitor lonafarnib, which showed potent inhibition of the RSV fusion process. Lonafarnib exhibited antiviral activity against both the RSV A and B genotypes and showed low cytotoxicity in HEp-2 and human primary bronchial epithelial cells (HBEC). Time-of-addition and pseudovirus assays demonstrated that lonafarnib inhibits RSV entry, but has farnesyltransferase-independent antiviral efficacy. Cryo-electron microscopy revealed that lonafarnib binds to a triple-symmetric pocket within the central cavity of the RSV F metastable pre-fusion conformation. Mutants at the RSV F sites interacting with lonafarnib showed resistance to lonafarnib but remained fully sensitive to the neutralizing monoclonal antibody palivizumab. Furthermore, lonafarnib dose-dependently reduced the replication of RSV in BALB/c mice. Collectively, lonafarnib could be a potential fusion inhibitor for RSV infection.

Abstract Recombinant adeno-associated viruses (rAAVs) have emerged as promising gene therapy vectors due to their proven efficacy and safety in clinical applications. In non-human primates (NHPs), rAAVs are administered via suprachoroidal injection at a higher dose. However, high doses of rAAVs tend to increase additional safety risks. Here, we present a novel AAV capsid (AAVv128), which exhibits significantly enhanced transduction efficiency for photoreceptors and retinal pigment epithelial (RPE) cells, along with a broader distribution across the layers of retinal tissues in different animal models (mice, rabbits, and NHPs) following intraocular injection. Notably, the suprachoroidal delivery of AAVv128-anti-VEGF vector completely suppresses the Grade IV lesions in a laser-induced choroidal neovascularization (CNV) NHP model for neovascular age-related macular degeneration (nAMD). Furthermore, cryo-EM analysis at 2.1 Å resolution reveals that the critical residues of AAVv128 exhibit a more robust advantage in AAV binding, the nuclear uptake and endosome escaping. Collectively, our findings highlight the potential of AAVv128 as a next generation ocular gene therapy vector, particularly using the suprachoroidal delivery route.

Abstract The SARS-CoV-2 Omicron variant evades most currently approved neutralizing antibodies (nAbs) and caused drastic decrease of plasma neutralizing activity elicited by vaccination or prior infection, urging the need for the development of pan-variant antivirals. Breakthrough infection induces a hybrid immunological response with potentially broad, potent and durable protection against variants, therefore, convalescent plasma from breakthrough infection may provide a broadened repertoire for identifying elite nAbs. We performed single-cell RNA sequencing (scRNA-seq) and BCR sequencing (scBCR-seq) of B cells from BA.1 breakthrough-infected patients who received 2 or 3 previous doses of inactivated vaccine. Elite nAbs, mainly derived from the IGHV2–5 and IGHV3-66/53 germlines, showed potent neutralizing activity across Wuhan-Hu-1, Delta, Omicron sublineages BA.1 and BA.2 at picomolar NT50 values. Cryo-EM analysis revealed diverse modes of spike recognition and guides the design of cocktail therapy. A single injection of paired antibodies cocktail provided potent protection in the K18-hACE2 transgenic female mouse model of SARS-CoV-2 infection.

The cause of seasonal hydrologic changes in tropical East Asia during interstadial/stadial oscillations of the last glaciation remains controversial. Here, we show seven seasonal drought events that occurred during the relatively warm interstadials by phytolith and pollen records. These events are significantly manifested as high percentages of bilobate phytoliths and are consistent with the large zonal sea-surface temperature (SST) gradient from the western to eastern tropical Pacific, suggesting that the reduction in seasonal precipitation could be interpreted by westward shifts of the western Pacific subtropical high triggered by changes of zonal SST gradient over the tropical Pacific and Hadley circulation in the Northern Hemisphere. Our findings highlight that both zonal and meridional ocean-atmosphere circulations, rather than solely the Intertropical Convergence Zone or El Niño-Southern Oscillation, controlled the hydrologic changes in tropical East Asia during the last glaciation. [ABSTRACT FROM AUTHOR]

Metafibers expand the functionalities of conventional optical fibres to unprecedented nanoscale light manipulations by integrating metasurfaces on the fibre tips, becoming an emerging light-coupling platform for both the nanoscience and fibre optics communities. Current metafibers remain proof-of-concept demonstrations that mostly explore isolated bare fibres owing to the lack of standard interfaces with universal fibre networks. Here, we develop methodologies for fabricating well-defined plasmonic metasurfaces directly on the end facets of commercial single -mode fibre jumpers using standard planar technologies and provide the first demonstration of their practical applications in the nonlinear plasmonic regime. Featuring plug-and-play connections with fibre circuitry and arbitrary metasurface landscapes, the metafibers with tunable plasmonic resonances are implemented into fibre laser cavities, yielding all-fibre sub-picosecond (minimum 513 fs) soliton mode locked lasers at optical wavelengths of 1.5 μm and 2 μm, demonstrating their unusual polarimetric nonlinear transfer functions and superior saturation absorption responses. The nanofabrication process flow is compatible with existing cleanroom technologies, offering metafibers an avenue to become a regular member of functionalised fibre components. This work paves the way toward the next generation of ultrafast lasers, optical frequency combs, and ultracompact ‘all-in-fibre’ optical systems.

Neutralizing antibodies are currently one versatile strategy to treat SARS-CoV-2 infection. Here, Li et al. characterize three monoclonal antibodies neutralizing authentic virus infection in vitro and in vivo by targeting the receptor binding domain as evidenced by Cryo-EM.

A general principle enabling the actuation of micro-objects on dry frictional surfaces based on opto-thermo-mechanical effects is established and two-dimensional spiral motions of gold plates on micro-fibers are experimentally demonstrated.

Cytochromes bd oxidase (Cyt-bd) catalyzes the reduction of oxygen to water and is the terminal oxidase in the respiratory chain of prokaryotes. Here, the authors present the 2.8 Å cryo-EM structure of Mycobacterium smegmatis Cyt-bd and identify two potential oxygen access channels in the structure, which is of interest for the development of novel antituberculosis drugs.

The established means of bandgap control in semiconductors are based on chemical, electrical or optical doping. Here, the authors report wide bandgap modulations in monolayer WS2 at room temperature by coupling the 2D semiconductor to a self-assembled plasmonic crystal inducing coherent hot electron doping.

Objective: Chronic inflammatory response plays a prominent role in obesity-related nonalcoholic fatty liver disease (NAFLD). However, the intrahepatic triggering mechanism of inflammation remains obscure. This study aimed to elucidate the role of serum amyloid A1 (SAA1), an acute-phase response protein, in the obesity-induced hepatic inflammation and NAFLD. Methods: Male mice were fed a high fat diet (HFD) for 16 weeks, and insulin resistance, hepatic steatosis, and inflammation in mice were monitored. Murine SAA1/2 was genetically manipulated to investigate the role of SAA1 in NAFLD. Results: We found that SAA1 was increased in the NAFLD liver in both humans and mice. Knockout of SAA1/2 or knockdown of hepatic SAA1/2 promoted energy expenditure and alleviated HFD-induced metabolic disorder, hepatic steatosis, and inflammation. Endogenous overexpression of SAA1 in hepatocytes by adeno-associated virus 8 (AAV8) transfection aggravated overnutrition-associated gain of body weight, insulin resistance, hepatic lipid accumulation, and liver injury, which were markedly alleviated by knockout of murine toll-like receptor 4 (TLR4). Mechanistically, SAA1 directly bound with TLR4/myeloid differentiation 2 (MD2) to induce TLR4 internalization, leading to the activation of nuclear factor (NF)-κB signaling and production of both SAA1 and other inflammatory cytokines, including interleukin (IL)-6 and C–C chemokine ligand (CCL2) in hepatocytes. Administration of HFD mice with an AAV8-shRNA-SAA1/2 showed a therapeutic effect on hepatic inflammation and NAFLD progression. Conclusions: These results demonstrate that SAA1 triggers hepatic steatosis and intrahepatic inflammatory response by forming a SAA1/TLR4/NF-κB/SAA1 feedforward regulatory circuit, which, in turn, leads to NAFLD progression. SAA1 may act as a potential target for the disease intervention.

Zhang, J., Lu, H., Wu, N., Li, F., Yang, X., Wang, W., Ma, M. & Zhang, X. 2010: Phytolith evidence for rice cultivation and spread in Mid-Late Neolithic archaeological sites in central North China. Boreas, Vol. 39, pp. 592–602. 10.1111/j.1502-3885.2010.00145.x. ISSN 0300-9483. The history of rice ( Oryza sativa) cultivation in North China is ambiguous owing to a lack of evidence from rice remains with precise ages in archaeological sites. In this paper, we present rice phytolith evidence from six archaeological sites in the Guanzhong Basin, central North China, dating from c. 5500 to 2100 cal. a BP (calibrated/calendar ages) based on 19 AMS-dates. The phytoliths found in the three archaeological sites located on the second river terrace (Quanhu, Yangguanzhai and Anban) include three types of phytoliths from rice, namely bulliform, parallel-bilobe and double-peaked. These findings suggest that the earliest cultivated rice in central North China occurred not later than c. 5690 cal. a BP. After c. 5500 cal. a BP, the farming pattern in the Guanzhong Basin was characterized by dominant dry crops (e.g. millets) and locally cultivated rice. A likely spread route of rice from the lower reaches of the Huanghe (Yellow) River towards the Guanzhong Basin in central North China is speculated to have happened at c. 5690 cal. a BP. The findings of this study help us to understand the farming pattern in the area and how rice spread across the semi-arid regions of East Asia. [ABSTRACT FROM AUTHOR]

Recently, the first late Miocene-Pliocene eolian deposits from the western Chinese Loess Plateau have been reported. These deposits would complement the eolian record between Quaternary loess-paleosol sequences and Miocene loess sequences, if their wind-blown origin could be documented. However, although several lines of evidence indicate the eolian origin of this sequence, it is still necessary to address this issue through further efforts. Among these, biological approaches are of particular value. Here we analyze the composition and preservation conditions of mollusk assemblages in the Dongwan section. Our results show that all mollusk fossil individuals are preserved in perfect condition without indicating any reworking. All identifiable mollusk species are terrestrial, and are mostly identical to those identified in the Quaternary loess-paleosol sequences of the Chinese Loess Plateau. Generally, the cold-aridiphilous species are dominant in the loess layers, while thermo-humidiphilous species are mostly encountered in the paleosols. The close similarity of the mollusk record in both the Dongwan late Miocene-Pliocene deposits and the Quaternary loess sequence in the Chinese Loess Plateau supports the supposition that the Dongwan section is a typical loess-paleosol sequence, and is, without any doubt, of wind-blown origin. [ABSTRACT FROM AUTHOR]

We demonstrate efficient ablation of metals with filamentary plasma grating generated by two intense blue femtosecond filaments and a third focused infrared pulse. This scheme leads to significant promotion of ablation efficiency on metal targets in air in comparison with single infrared or blue filament with equal pulse energy. The reason is that the blue plasma grating firstly provides stronger intensity and a higher density of background electrons, then the delayed infrared pulse accelerates local electrons inside the plasma grating. These two processes finally results in robustly increased electron density and highly ionized metallic atoms.